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Link to original content: http://pubmed.ncbi.nlm.nih.gov/37439814/
Developmental brain lipidomics is influenced by postnatal chlorpyrifos exposure and APOE genetic background in mice - PubMed Skip to main page content
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. 2023 Sep;97(9):2463-2475.
doi: 10.1007/s00204-023-03555-8. Epub 2023 Jul 13.

Developmental brain lipidomics is influenced by postnatal chlorpyrifos exposure and APOE genetic background in mice

Laia Guardia-Escote  1   2 , Judit Biosca-Brull  1   2   3 , Maria Cabré  1   4 , Jordi Blanco  1   3   5 , Mikaela Mladenova-Koleva  1 , Pia Basaure  1 , Cristian Pérez-Fernández  6 , Fernando Sánchez-Santed  6 , José L Domingo  3 , Maria Teresa Colomina  7   8   9
Affiliations

Developmental brain lipidomics is influenced by postnatal chlorpyrifos exposure and APOE genetic background in mice

Laia Guardia-Escote et al. Arch Toxicol. 2023 Sep.

Abstract

Lipids are a major component of the brain, and are involved in structural and neurodevelopmental processes such as neurogenesis, synaptogenesis and signaling. Apolipoprotein E (apoE) is the main lipoprotein involved in lipid transport in the brain. The apoE isoforms can determine vulnerability to the toxic effects of the pesticide chlorpyrifos (CPF), which can interfere with normal neurodevelopment. We aimed to study the effects of postnatal exposure to CPF and of the APOE genotype on the lipid composition of the brain at early ages. For it, we used apoE3 and apoE4 targeted-replacement (TR) male mice, as well as wild-type C57BL/6. The mice were orally exposed to 1 mg/kg/day of CPF on postnatal days 10-15 and, four hours after the treatment, we obtained samples to assess the cerebral lipid composition. Differences between APOE genotypes were found in the cerebral lipid profile in the postnatal period. ApoE4-TR mice exhibited higher lipid concentrations compared to the other groups in most of the cases. CPF exposure led to a decrease in cholesteryl ester and triglyceride concentrations, while modulating the levels of phosphatidylcholine species based on the apoE isoform. Specifically, CPF treatment decreased the concentration of some species of this lipid (PC30:0, PC31:0, PC32:2, PC36:5, PC40:4 and PC40:5) in C57BL/6 mice exposed to CPF, increased (PC31:0 and PC37:6) in apoE3-TR exposed mice while exposed apoE4-TR mice remained unaltered. These results provide further insights into the lipid composition of the brain at early ages, and how it can be modulated by environmental and genetic factors.

Keywords: APOE; Brain development; Chlorpyrifos; Lipidomics.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Cholesteryl ester (ChoE) profile in mouse brain. Heatmap of the brain concentration (pmol/mg tissue) of the ChoE species for each experimental group (A). ChoE species presenting significant differences between genotypes (B–F) and treatments (G). All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 2
Fig. 2
Cholesteryl ester (ChoE) species presenting a significant interaction between genotype and treatment. All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 3
Fig. 3
Diglyceride (DG) profile in mouse brain. Heatmap of the brain concentration (pmol/mg tissue) of the DG species for each experimental group (A). DG species presenting significant differences between genotype (B–D). All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 4
Fig. 4
Lysoposphocholine (LPC) profile in mouse brain. Heatmap of the brain concentration (pmol/mg tissue) of the LPC species for each experimental group (A). LPC species presenting significant differences between genotypes (B–E). All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 5
Fig. 5
Phosphatidylcholine (PC) profile in mouse brain. Heatmap of the brain concentration (pmol/mg tissue) of the PC species for each experimental group (A). PC species presenting significant differences between genotypes (B–M). All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 6
Fig. 6
Phosphatidylcholine (PC) species presenting a significant interaction between genotype and treatment. All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 7
Fig. 7
Phosphatidylethanolamine (PE) profiles in mouse brain. Heatmap of the brain concentration (pmol/mg tissue) of the PE species for each experimental group. All groups included six animals except for the apoE4-CNT, which included five. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 8
Fig. 8
Sphingomyelin (SM) profile in mouse brain. Heatmap of the brain concentration (pmol/mg tissue) of the SM species for each experimental group (A). SM species presenting significant differences between genotypes (B–C). All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 9
Fig. 9
Triglyceride (TG) profiles in mouse brain. Heatmap of the brain concentration (pmol/mg tissue) of the TG species for each experimental group (A). TG species presenting significant differences between genotypes (B–G). All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05. Abbreviations: CNT control, CPF chlorpyrifos-treated
Fig. 10
Fig. 10
Triglyceride (TG) species presenting significant differences between treatments. All groups included six animals except for the apoE4-CNT, which included five. An asterisk (*) indicates significant differences between groups at p < 0.05
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